Synthesis And Application Of The Novel Branched Polyethylene Glycol For Low Molecular Weight Medicine Modification

Chemical modification is a kind of method to prove the pharmacological property of a medicine by changing its structure with the connection of a modifier in chemical reaction. Many kinds of alternative modifiers have been achieved, and polyethylene glycol(PEG) derivatives have been extensively used in chemical modification due to its well solubility, biocompatibility and immunogenicity. In this dissertation, several PEG derivatives are synthesized, and two kinds of PEG derivatives which derived from PEG and citric acid or malic acid with multiple active functional groups for potential better carrying capacity have not been reported in literatures to our knowledge. The synthetic products were characterized by infrared spectrum and nuclear magnetic resonance analysis. The results of characterization are consistent with the structures of the product.In order to review the effect of modification, one PEG derivative synthesized were applied to the modification of taxol. The physical properties of taxol and the prodrugs, such as drug load capacity (i.e. the amount of taxol) and aqueous solubility were determined. The results show that the new produg's drug load capacity and aqueous solubility have been greatly improved than taxol.The in vitro inhibition activity of taxol prodrugs against SW1990 human pancreatic cancer cell lines was investigated. The IC50 index indicated that the new prodrug showed better anti-tumor activities on the tumor model. Compared with taxol, the efficiency of the prodrug was even more satisfied in the primary trial result. The comprehensive analysis suggests that the new branched prodrug is a promising water-soluble taxol prodrug with great potential of application.